10-76885239-T-TTA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001161352.2(KCNMA1):c.*2026_*2027insTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000418 in 480,628 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: KCNMA1 NM_001161352.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.715

Genes affected

KCNMA1 (HGNC:6284): (potassium calcium-activated channel subfamily M alpha 1) This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00103 (152/147468) while in subpopulation EAS AF= 0.0176 (90/5122). AF 95% confidence interval is 0.0146. There are 1 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.*2026_*2027insTA		3_prime_UTR_variant	28/28	ENST00000286628.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.*2026_*2027insTA		3_prime_UTR_variant	28/28	1	NM_001161352.2	A2

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 152 AN: 147468 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000679

Gnomad ASJ AF: 0.00174

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000895

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000147 AC: 49 AN: 333160 Hom.: 0 Cov.: 5 AF XY: 0.000138 AC XY: 22 AN XY: 159154

Gnomad4 AFR exome AF: 0.000821

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00244

Gnomad4 EAS exome AF: 0.0108

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000298

Gnomad4 OTH exome AF: 0.000267

GnomAD4 genome AF: 0.00103 AC: 152 AN: 147468 Hom.: 1 Cov.: 30 AF XY: 0.00107 AC XY: 77 AN XY: 71860

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.0000679

Gnomad4 ASJ AF: 0.00174

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.000421

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000895

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Generalized epilepsy-paroxysmal dyskinesia syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs562756117; hg19: chr10-78644997;